Streptococcus are gram (+) bacteria that are differentiated by group specific carbohydrate antigens A through O found on their cell surface. Streptococcus groups are further distinguished by type-specific capsular polysaccharide antigens. Several serotypes have been identified for the GBS: Ia, Ib, II, III, IV, V, VI, VII and VIII. GBS also contains antigenic proteins known as “C-proteins” (alpha, beta, gamma and delta), some of which have been cloned.
Although GBS is a common component of the normal human vaginal and colonic flora this pathogen has long been recognized as a major cause of infections in neonates, expectant mothers, some non-pregnant adults as well as mastitis in dairy herds. Expectant mothers exposed to GBS are at risk of postpartum infection and may transfer the infection to their baby as the child passes through the birth canal.
GBS infections in infants are restricted to very early infancy. Approximately 80% of infant infections occur in the first days of life, so-called early-onset disease. Late-onset infections occur in infants between 1 week and 2 to 3 months of age. Clinical syndromes of GBS disease in newborns include sepsis, meningitis, pneumonia, cellulitis, osteomyelitis, septic arthritis, endocarditis and epiglottis. In addition to acute illness due to GBS, which is itself costly, GBS infections in newborns can result in death, disability, and, in rare instances, recurrence of infection. Although the organism is sensitive to antibiotics, the high attack rate and rapid onset of sepsis in neonates and meningitis in infants results in high morbidity and mortality.
Among pregnant women, GBS causes clinical illness ranging from mild urinary tract infection to life-threatening sepsis and meningitis, including also osteomyelitis, endocarditis, amnionitis, endometritis, wound infections (postcesarean and postepisiotomy), cellulitis, fasciitis.
Among non-pregnant adults, the clinical presentations of invasive GBS disease most often take the form of primary bacteremia but also skin or soft tissue infection, pneumonia, urosepsis, endocarditis, peritonitis, meningitis, empyema. Skin or soft tissue infections include cellulitis, infected peripheral ulcers, osteomyelitis, septic arthritis and decubiti or wound infections. Among people at risk, there are debilitated hosts such as people with a chronic disease such as diabetes mellitus and cancer, or elderly people.
GBS infections can also occur in animals and cause mastitis in dairy herds.
Type-specific polysaccharides have proven to be poorly immunogenic in hosts and are restricted to the particular serotype from which the polysaccharide originates. Further, capsular polysaccharide elicit a T cell independent response i.e., no IgG production. Consequently capsular polysaccharide antigens are unsuitable as a vaccine component for protection against GBS infection.
Others have focused on the C-protein beta antigen which demonstrated immunogenic properties in mice and rabbit models. This protein was found to be unsuitable as a human vaccine because of its undesirable property of interacting with high affinity and in a non-immunogenic manner with the Fc region of human IgA. The C-protein alpha antigen is rare in type III serotypes of GBS which is the serotype responsible for most GBS mediated conditions and is therefore of little use as a vaccine component.
There remains an unmet need for GBS polypeptides which may be used to prevent, diagnose and/or treat GBS infection.